Effects of Maternal Blood Levels of One‐carbon Nutrients on Global DNA Methylation and Demethylation in Cord Blood Lymphocytes

Abstract

DNA methylation is an important epigenetic determinant in gene expression, with potential consequent effects on disease susceptibility. During embryogenesis, new DNA methylation patterns of the fetus are established, rendering this period highly susceptible to environmental modifiers. Maternal dietary intake of one-carbon nutrients (folate, B6, B12, choline, and betaine) have the potential to modulate DNA methylation via the provision of S-adenosylmethionine. We determined the relationship between maternal blood levels of one-carbon nutrients and 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC; a proxy for demethylation) contents in cord blood lymphocyte DNA using LC/MS-MS in 291 Canadian mother-child pairs. Mean(SD) % of 5mC and 5hmC were 5.5(0.4)% and 0.03(0.02)%, respectively. 5mC contents were weakly correlated with maternal B12 levels at baseline (~12 wks gestation) (r=0.19, p<0.01) and B6 levels at delivery (r=0.13, p=0.04). Baseline maternal (r=-0.15, p=0.01) and cord blood (r=-0.13, p=0.03) RBC folate levels were inversely and maternal B6 levels at delivery (r=0.13, p=0.04) and baseline maternal betaine levels (r=0.13, p=0.03) were positively associated with 5hmC contents. These data suggest maternal blood levels of one-carbon nutrients can influence DNA methylation and demethylation of the fetus. Further studies are warranted to explore functional ramifications of changes in DNA methylation and demethylation in the offspring resulting from maternal nutrient status. Funded by: CIHR (MOP# 106446)